The Effect of Triheptanoin on Fatty Acid Oxidation and Exercise Tolerance in Patients With Glycogenoses
NCT ID: NCT03642860
Last Updated: 2024-02-22
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
3 participants
Study Classification
INTERVENTIONAL
Study Start Date
2018-08-15
Study Completion Date
2019-08-28
Brief Summary
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The aim of this study is to investigate the effect of 14 days of treatment with the dietary oil-supplement Triheptanoin on fat metabolism and exercise tolerance in patients with Phosphofructokinase deficiency, Debrancher deficiency and Glycogenin-1 deficiency. The investigators wish to investigate whether a Triheptanoin diet can improve exercise capacity by measuring:
1. Heart rate during cycling exercise and maximal exercise capacity
2. Fat and glucose metabolism
3. Concentrations of metabolic substrates in blood during exercise
4. Perception of fatigue and symptoms by questionnaire
5. Degree of exhaustion during cycling exercise by Borg score
All measurements are done before and after 14 days with a Triheptanoin-oil diet, and before and after 14 days diet with safflower (Placebo-oil).
Triheptanoin-oil supplementation in the diet has been shown to increase metabolism of both fat and carbohydrates in patients with other metabolic myopathies. In these patients, Triheptanoin improved physical performance and has reduced the amount of symptoms experienced by patients.
1. Heart rate during cycling exercise and maximal exercise capacity
2. Fat and glucose metabolism
3. Concentrations of metabolic substrates in blood during exercise
4. Perception of fatigue and symptoms by questionnaire
5. Degree of exhaustion during cycling exercise by Borg score
All measurements are done before and after 14 days with a Triheptanoin-oil diet, and before and after 14 days diet with safflower (Placebo-oil).
Triheptanoin-oil supplementation in the diet has been shown to increase metabolism of both fat and carbohydrates in patients with other metabolic myopathies. In these patients, Triheptanoin improved physical performance and has reduced the amount of symptoms experienced by patients.
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Detailed Description
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BACKGROUND:
Neuromuscular diseases affect more than 5% of the population in Western countries. Some of the more rare neuromuscular disorders are patients with metabolic myopathies, which are hereditary disorders caused by enzymatic defects of intermediary metabolism. The disorders are generally subdivided in two major groups affecting either carbohydrate metabolism (the glycogenosis) or lipid metabolism. Patients suffer from recurrent episodes of exercise intolerance, muscle pain and muscle contractures/stiffness, and in severe cases rhabdomyolysis (breakdown of skeletal muscle fibers) and myoglobinuria. Recognition of the metabolic block in the metabolic myopathies has started the development of new therapeutic options. Enzyme replacement therapy with recombinant lysosomal acid alpha-glucosidase (rGAA) has revolutionized treatment of early onset Pompe's disease, glycogen storage disease (GSD) II.(1-3) Supplements of riboflavin, carnitine and sucrose show promise in patients with respectively riboflavin-responsive multiple acyl-Coenzyme A (CoA) dehydrogenase deficiency (4), primary carnitine deficiency (5-7) and McArdle disease (8). However, for many of the glycogenosis treatment primarily relies on avoiding precipitating factors, and dietary supplements that bypass the metabolic block.(9) Only a few of the used supplements are validated, and further studies are needed to define efficacious treatments.
A promising product for treatment of glycogenosis is Triheptanoin. Triheptanoin provides patients with medium-length, odd-chain fatty acids that are metabolized into ketones, which replace deficient intermediates in the Tricaboxylic acid (TCA) cycle, thus supporting glucose production through gluconeogenesis, resulting in a lower turnover of glycogen.(10) Triheptanoin has primarily been used in lipid metabolism disorders, where it has shown a remarkable improvement of cardiac and muscular symptoms in three children with VLCAD deficiency and in seven patients with Carnitine palmitoyltransferase (CPT) II deficiency after dietary Triheptanoin supplementation.(10,11)
Metabolic studies in patients with the glycogenosis McArdle disease and Debrancher deficiency has showed that these disorders are associated with an energy deficit caused by reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation. Despite increasing availability of free fatty acid (FFA) during exercise, fatty acid oxidation (FAO) is not increased further, even though the energy deficit is maintained.(12,13)
McArdle disease is one of the largest and most investigated groups of the muscle glycogenosis, caused by mutations in the myophosphorylase gene (PYGM) on chromosome 11 that encodes muscle glycogen phosphorylase.(14). It is know that TCA cycle intermediates are low during exercise in patients with McArdle disease, and most likely the impaired FAO relates to a slowing of the TCA-cycle by limited supply from glycolysis.(15) Triheptanoin, most likely can correct the suspected shortage of anaplerotic intermediates to spark the TCA-cycle in patients with glycogenosis as well, and studies are ongoing in patients with McArdle disease at our research unit Copenhagen Neuromuscular Center. Clinical-Trials.gov Identifier: NCT02432768.
Other glycogenoses as Debrancher deficiency, Phosphofructokinase deficiency and Glycogenin 1 deficiency, all involved in either glycogenolysis or gluconeogenesis might benefit from Triheptanoin treatment.
Glycogen storage disease III (GSD III) also known as Debrancher deficiency or Cori-Forbes disease is caused by deficient activity of glycogen debranching enzyme (GDE) due to mutations in the AGL gene on chromosome 1p21. (16) More than 20 different disease-causing mutations have been identified in this gene.(17) Debranching enzyme is required for complete hydrolysis of glycogen and GSD III is associated with an accumulation of abnormal glycogen with short outer chains.(18) Four subtypes are described:
1. Type IIIa (the most common) that affects enzymes in the liver and the skeletal and cardiac muscle.
2. Type IIIb (about 15% of patients) involves only the liver enzyme.
3. Type IIIc (rare) with a selective loss of only one of the two GDE activities affecting muscle.
4. Type IIId (rare) with loss of the transferase affecting muscle and liver (19) Dominant features during infancy and childhood are hepatomegaly, hypoglycaemia, hyperlipidaemia, and growth retardation.(16) Muscle weakness (myopathy) and wasting typically present in the third decade. Weakness can be both proximal and distal. Electromyography (EMG) and muscle histology show myopathic changes and large glycogen deposits in the muscle.(20) Treatment is symptomatic. GSD III is associated with fixed skeletal muscle weakness and some patients have exercise-related dynamic symptoms, most likely caused by a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation.(13,21) Phosphofructokinase deficiency (GSD VII) is another glycogenosis inherited in an autosomal recessive manner causing a defect in the rate-limiting enzyme of glycolysis, phosphofructokinase (PFK).(22) The defect results in a complete block in muscle glycolysis and glycogenolysis. Clinical features are exercise intolerance, myopathy and muscle contractures that can lead to myoglobinuria. The exercise intolerance is due to a severely restricted oxidative metabolism. An increase in blood glucose will actually decrease exercise tolerance in GSD VII contrary to GSD IIIa where it has an increasing effect. Therefore, the GSD VII subjects depend on the availability of blood borne fuels such as free fatty acids and ketones seen during fasting. (23) Glycogenin-1(GYG1) deficiency (GSD XV) (OMIM #613507) is an inborn error of glycogen synthesis caused by mutations in the GYG1 gene. GYG1 works as the initial building block in the biosynthesis of glycogen in skeletal muscle. It is a glycosyl-transferase that uses UDP-glucose as substrate for autoglycosylation, forming an oligosaccharide by the process of UDP-alpha-D-glucose + glycogenin -\> UDP + alpha-D-glucosylglycogenin.(24) GYG1 deficiency is inherited autosomal recessively, and is the most recently discovered muscle glycogenosis.
Most patients present with a slowly progressive adult-onset myopathy with a variable clinical presentation.(25) Some adult patients also report exercise intolerance.(26-28) Metabolic studies show that patients with GYG1 deficiency, not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion; results are accepted for publication in Neurology.
At present, there is only 1 known patient with Debrancher deficiency, no patients with PFK deficiency and two patients with GYG1 deficiency in Denmark. Therefore the study will aim to include patients from abroad. Patients will fly in for studies in Copenhagen, as the investigators have done many times before.(12,29-31)
Based on observation from Roe et al. and Mochel et al. the first effects of Triheptanoin appears within 48 hrs of treatment. Furthermore, based on these observations the treatment period will consist of a week of dosage escalation to avoid potential gastro-intestinal side effects.(10,11,32-34) Therefore, the investigators hypothesize that 14 days of treatment with Triheptanoin oil will improve exercise tolerance, indicated by heart rate, and fatty acid oxidation during steady state cycling exercise using indirect calorimetry and stable isotope technique in patients with the glycogenosis Debrancher deficiency, PFK deficiency and GYG1 deficiency.
INVESTIGATIONAL PRODUCT:
UX007 (Triheptanoin) is an artificially made oil of a triglyceride of three 7-carbon fatty acid chains (heptanoate) that can be used in the treatment of patients with several types of inborn errors of metabolism associated with an impaired functioning of the TCA.(10,11,32-34)(See Investigator's Brochure). UX007 (Triheptanoin) is a liquid, intended for PO administration. UX007 is a colorless to yellow oil supplied in 1 L round amber-colored glass bottles. UX007 is manufactured, packaged, and labeled according to Good Manufacturing Procedure (GMP) regulations.
Processes that replenish the stores of TCA-intermediates are called anaplerosis. Metabolism of odd-numbered carbon fatty acids such as Triheptanoin provides anaplerotic substrates through ketone body production in the liver and beta-oxidation in peripheral tissues, which forms propionyl- and acetyl-CoA that both enter the TCA-cycle.(32-35) The effect of the UX007-intake will be compared to intake of a placebo substance. Placebo will consist of safflower oil and will match the appearance of UX007, which is orally administered in the same manner as UX007.
Neuromuscular diseases affect more than 5% of the population in Western countries. Some of the more rare neuromuscular disorders are patients with metabolic myopathies, which are hereditary disorders caused by enzymatic defects of intermediary metabolism. The disorders are generally subdivided in two major groups affecting either carbohydrate metabolism (the glycogenosis) or lipid metabolism. Patients suffer from recurrent episodes of exercise intolerance, muscle pain and muscle contractures/stiffness, and in severe cases rhabdomyolysis (breakdown of skeletal muscle fibers) and myoglobinuria. Recognition of the metabolic block in the metabolic myopathies has started the development of new therapeutic options. Enzyme replacement therapy with recombinant lysosomal acid alpha-glucosidase (rGAA) has revolutionized treatment of early onset Pompe's disease, glycogen storage disease (GSD) II.(1-3) Supplements of riboflavin, carnitine and sucrose show promise in patients with respectively riboflavin-responsive multiple acyl-Coenzyme A (CoA) dehydrogenase deficiency (4), primary carnitine deficiency (5-7) and McArdle disease (8). However, for many of the glycogenosis treatment primarily relies on avoiding precipitating factors, and dietary supplements that bypass the metabolic block.(9) Only a few of the used supplements are validated, and further studies are needed to define efficacious treatments.
A promising product for treatment of glycogenosis is Triheptanoin. Triheptanoin provides patients with medium-length, odd-chain fatty acids that are metabolized into ketones, which replace deficient intermediates in the Tricaboxylic acid (TCA) cycle, thus supporting glucose production through gluconeogenesis, resulting in a lower turnover of glycogen.(10) Triheptanoin has primarily been used in lipid metabolism disorders, where it has shown a remarkable improvement of cardiac and muscular symptoms in three children with VLCAD deficiency and in seven patients with Carnitine palmitoyltransferase (CPT) II deficiency after dietary Triheptanoin supplementation.(10,11)
Metabolic studies in patients with the glycogenosis McArdle disease and Debrancher deficiency has showed that these disorders are associated with an energy deficit caused by reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation. Despite increasing availability of free fatty acid (FFA) during exercise, fatty acid oxidation (FAO) is not increased further, even though the energy deficit is maintained.(12,13)
McArdle disease is one of the largest and most investigated groups of the muscle glycogenosis, caused by mutations in the myophosphorylase gene (PYGM) on chromosome 11 that encodes muscle glycogen phosphorylase.(14). It is know that TCA cycle intermediates are low during exercise in patients with McArdle disease, and most likely the impaired FAO relates to a slowing of the TCA-cycle by limited supply from glycolysis.(15) Triheptanoin, most likely can correct the suspected shortage of anaplerotic intermediates to spark the TCA-cycle in patients with glycogenosis as well, and studies are ongoing in patients with McArdle disease at our research unit Copenhagen Neuromuscular Center. Clinical-Trials.gov Identifier: NCT02432768.
Other glycogenoses as Debrancher deficiency, Phosphofructokinase deficiency and Glycogenin 1 deficiency, all involved in either glycogenolysis or gluconeogenesis might benefit from Triheptanoin treatment.
Glycogen storage disease III (GSD III) also known as Debrancher deficiency or Cori-Forbes disease is caused by deficient activity of glycogen debranching enzyme (GDE) due to mutations in the AGL gene on chromosome 1p21. (16) More than 20 different disease-causing mutations have been identified in this gene.(17) Debranching enzyme is required for complete hydrolysis of glycogen and GSD III is associated with an accumulation of abnormal glycogen with short outer chains.(18) Four subtypes are described:
1. Type IIIa (the most common) that affects enzymes in the liver and the skeletal and cardiac muscle.
2. Type IIIb (about 15% of patients) involves only the liver enzyme.
3. Type IIIc (rare) with a selective loss of only one of the two GDE activities affecting muscle.
4. Type IIId (rare) with loss of the transferase affecting muscle and liver (19) Dominant features during infancy and childhood are hepatomegaly, hypoglycaemia, hyperlipidaemia, and growth retardation.(16) Muscle weakness (myopathy) and wasting typically present in the third decade. Weakness can be both proximal and distal. Electromyography (EMG) and muscle histology show myopathic changes and large glycogen deposits in the muscle.(20) Treatment is symptomatic. GSD III is associated with fixed skeletal muscle weakness and some patients have exercise-related dynamic symptoms, most likely caused by a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation.(13,21) Phosphofructokinase deficiency (GSD VII) is another glycogenosis inherited in an autosomal recessive manner causing a defect in the rate-limiting enzyme of glycolysis, phosphofructokinase (PFK).(22) The defect results in a complete block in muscle glycolysis and glycogenolysis. Clinical features are exercise intolerance, myopathy and muscle contractures that can lead to myoglobinuria. The exercise intolerance is due to a severely restricted oxidative metabolism. An increase in blood glucose will actually decrease exercise tolerance in GSD VII contrary to GSD IIIa where it has an increasing effect. Therefore, the GSD VII subjects depend on the availability of blood borne fuels such as free fatty acids and ketones seen during fasting. (23) Glycogenin-1(GYG1) deficiency (GSD XV) (OMIM #613507) is an inborn error of glycogen synthesis caused by mutations in the GYG1 gene. GYG1 works as the initial building block in the biosynthesis of glycogen in skeletal muscle. It is a glycosyl-transferase that uses UDP-glucose as substrate for autoglycosylation, forming an oligosaccharide by the process of UDP-alpha-D-glucose + glycogenin -\> UDP + alpha-D-glucosylglycogenin.(24) GYG1 deficiency is inherited autosomal recessively, and is the most recently discovered muscle glycogenosis.
Most patients present with a slowly progressive adult-onset myopathy with a variable clinical presentation.(25) Some adult patients also report exercise intolerance.(26-28) Metabolic studies show that patients with GYG1 deficiency, not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion; results are accepted for publication in Neurology.
At present, there is only 1 known patient with Debrancher deficiency, no patients with PFK deficiency and two patients with GYG1 deficiency in Denmark. Therefore the study will aim to include patients from abroad. Patients will fly in for studies in Copenhagen, as the investigators have done many times before.(12,29-31)
Based on observation from Roe et al. and Mochel et al. the first effects of Triheptanoin appears within 48 hrs of treatment. Furthermore, based on these observations the treatment period will consist of a week of dosage escalation to avoid potential gastro-intestinal side effects.(10,11,32-34) Therefore, the investigators hypothesize that 14 days of treatment with Triheptanoin oil will improve exercise tolerance, indicated by heart rate, and fatty acid oxidation during steady state cycling exercise using indirect calorimetry and stable isotope technique in patients with the glycogenosis Debrancher deficiency, PFK deficiency and GYG1 deficiency.
INVESTIGATIONAL PRODUCT:
UX007 (Triheptanoin) is an artificially made oil of a triglyceride of three 7-carbon fatty acid chains (heptanoate) that can be used in the treatment of patients with several types of inborn errors of metabolism associated with an impaired functioning of the TCA.(10,11,32-34)(See Investigator's Brochure). UX007 (Triheptanoin) is a liquid, intended for PO administration. UX007 is a colorless to yellow oil supplied in 1 L round amber-colored glass bottles. UX007 is manufactured, packaged, and labeled according to Good Manufacturing Procedure (GMP) regulations.
Processes that replenish the stores of TCA-intermediates are called anaplerosis. Metabolism of odd-numbered carbon fatty acids such as Triheptanoin provides anaplerotic substrates through ketone body production in the liver and beta-oxidation in peripheral tissues, which forms propionyl- and acetyl-CoA that both enter the TCA-cycle.(32-35) The effect of the UX007-intake will be compared to intake of a placebo substance. Placebo will consist of safflower oil and will match the appearance of UX007, which is orally administered in the same manner as UX007.
Conditions
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Tarui Disease
Debrancher Deficiency
GYG1 DEFICIENCY
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
The study will be conducted as a randomized, placebo-controlled, double blind, crossover study consisting of two 14 days treatment periods set apart by minimum a 7-days wash-out period where no treatment is taken. In one treatment period, the subjects receive UX007 treatment and placebo treatment in the other. The study will consist of three separate groups; one group consisting of GSD III, one group of GSD VII, and one group of GSD XV subjects. Each of these groups will be blinded and randomized separately
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Study Groups
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Active treatment
Triheptanoin oil
Group Type
EXPERIMENTAL
Triheptanoin
Intervention Type
DRUG
Daily treatment with Triheptanoin oil for 14 days (7 days titration period in addition to 7 days full dose period with 1g/kg/day).
Placebo treatment
Safflower oil
Group Type
PLACEBO_COMPARATOR
Placebo Oil
Intervention Type
DRUG
Daily treatment with Safflower oil for 14 days (7 days titration period in addition to 7 days full dose period with 1g/kg/day).
Interventions
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Triheptanoin
Daily treatment with Triheptanoin oil for 14 days (7 days titration period in addition to 7 days full dose period with 1g/kg/day).
Intervention Type
DRUG
Placebo Oil
Daily treatment with Safflower oil for 14 days (7 days titration period in addition to 7 days full dose period with 1g/kg/day).
Intervention Type
DRUG
Other Intervention Names
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Trioctanoin
Eligibility Criteria
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Inclusion Criteria
* Males and females age \>15 years
* Genetically and/or biochemically verified diagnosis of Debrancher deficiency or Phosphofructokinase deficiency or Glycogenin 1 deficiency
* Capacity to consent
* All women in fertile age must be on contraceptive treatment with: Birth control pills, coil, ring, transdermal hormone patch injection of synthetic progesterone or subdermal implant.
* Genetically and/or biochemically verified diagnosis of Debrancher deficiency or Phosphofructokinase deficiency or Glycogenin 1 deficiency
* Capacity to consent
* All women in fertile age must be on contraceptive treatment with: Birth control pills, coil, ring, transdermal hormone patch injection of synthetic progesterone or subdermal implant.
Exclusion Criteria
* Significant cardiac or pulmonary disease
* Pregnancy (confirmed by urine stick) or breastfeeding.
* Treatment with beta-blockers
* Inability to perform cycling exercise
* Any other significant disorder that may confound the interpretation of the findings.
* Subjects at risk of musculoskeletal injury, i.e. with disease in joints or muscle.
* Pregnancy (confirmed by urine stick) or breastfeeding.
* Treatment with beta-blockers
* Inability to perform cycling exercise
* Any other significant disorder that may confound the interpretation of the findings.
* Subjects at risk of musculoskeletal injury, i.e. with disease in joints or muscle.
Minimum Eligible Age
15 Years
Maximum Eligible Age
85 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Ultragenyx Pharmaceutical Inc
INDUSTRY
Sponsor Role
collaborator
Rigshospitalet, Denmark
OTHER
Sponsor Role
lead
Responsible Party
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Mette Cathrine Oerngreen
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Locations
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Copenhagen Neuromuscular Center
Copenhagen, , Denmark
Site Status
Countries
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Denmark
References
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Harris, R. & Devlin, T. Textbook of Biochemistry with Clinical Correlations. 1997, (Wiley-Liss).
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RESULT
Orngreen MC, Vissing J. Treatment Opportunities in Patients With Metabolic Myopathies. Curr Treat Options Neurol. 2017 Sep 21;19(11):37. doi: 10.1007/s11940-017-0473-2.
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RESULT
Roe CR, Sweetman L, Roe DS, David F, Brunengraber H. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. J Clin Invest. 2002 Jul;110(2):259-69. doi: 10.1172/JCI15311.
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RESULT
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Reference Type
RESULT
Preisler N, Laforet P, Madsen KL, Prahm KP, Hedermann G, Vissing CR, Galbo H, Vissing J. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III. Neurology. 2015 Apr 28;84(17):1767-71. doi: 10.1212/WNL.0000000000001518. Epub 2015 Apr 1.
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RESULT
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RESULT
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Malfatti E, Nilsson J, Hedberg-Oldfors C, Hernandez-Lain A, Michel F, Dominguez-Gonzalez C, Viennet G, Akman HO, Kornblum C, Van den Bergh P, Romero NB, Engel AG, DiMauro S, Oldfors A. A new muscle glycogen storage disease associated with glycogenin-1 deficiency. Ann Neurol. 2014 Dec;76(6):891-8. doi: 10.1002/ana.24284. Epub 2014 Oct 31.
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Akman HO, Aykit Y, Amuk OC, Malfatti E, Romero NB, Maioli MA, Piras R, DiMauro S, Marrosu G. Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1. Neuromuscul Disord. 2016 Jan;26(1):16-20. doi: 10.1016/j.nmd.2015.10.012. Epub 2015 Nov 10.
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Luo S, Zhu W, Yue D, Lin J, Wang Y, Zhu Z, Qiu W, Lu J, Hedberg-Oldfors C, Oldfors A, Zhao C. Muscle pathology and whole-body MRI in a polyglucosan myopathy associated with a novel glycogenin-1 mutation. Neuromuscul Disord. 2015 Oct;25(10):780-5. doi: 10.1016/j.nmd.2015.07.007. Epub 2015 Jul 15.
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Orngreen MC, Madsen KL, Preisler N, Andersen G, Vissing J, Laforet P. Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized clinical trial. Neurology. 2014 Feb 18;82(7):607-13. doi: 10.1212/WNL.0000000000000118. Epub 2014 Jan 22.
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ORngreen MC, Norgaard MG, Sacchetti M, van Engelen BG, Vissing J. Fuel utilization in patients with very long-chain acyl-coa dehydrogenase deficiency. Ann Neurol. 2004 Aug;56(2):279-83. doi: 10.1002/ana.20168.
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Orngreen MC, Schelhaas HJ, Jeppesen TD, Akman HO, Wevers RA, Andersen ST, ter Laak HJ, van Diggelen OP, DiMauro S, Vissing J. Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency? Neurology. 2008 May 13;70(20):1876-82. doi: 10.1212/01.wnl.0000289190.66955.67. Epub 2008 Apr 9.
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Roe CR, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):332-40. doi: 10.1007/s10545-006-0290-3.
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Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D, Roe CR, Saudubray JM. Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. Mol Genet Metab. 2005 Apr;84(4):305-12. doi: 10.1016/j.ymgme.2004.09.007.
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Roe CR, Bottiglieri T, Wallace M, Arning E, Martin A. Adult Polyglucosan Body Disease (APBD): Anaplerotic diet therapy (Triheptanoin) and demonstration of defective methylation pathways. Mol Genet Metab. 2010 Oct-Nov;101(2-3):246-52. doi: 10.1016/j.ymgme.2010.06.017. Epub 2010 Jul 6.
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Brunengraber H, Roe CR. Anaplerotic molecules: current and future. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):327-31. doi: 10.1007/s10545-006-0320-1.
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RESULT
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2017-004153-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
#20171012 Trihep
Identifier Type: -
Identifier Source: org_study_id
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